8-3333348-G-T

Variant names:

• chr8-3333348-G-T
• rs4395910
• NM_033225.6:c.3631+9946C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033225.6(CSMD1):​c.3631+9946C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 152,060 control chromosomes in the GnomAD database, including 26,693 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.58 (26693 hom., cov: 33)
• Consequence: CSMD1 NM_033225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• Publications: 1 publications found

Genes affected

CSMD1 (HGNC:14026): (CUB and Sushi multiple domains 1) Predicted to act upstream of or within several processes, including learning or memory; mammary gland branching involved in pregnancy; and reproductive structure development. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

CSMD1 Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSMD1	NM_033225.6	c.3631+9946C>A		intron_variant	Intron 23 of 69	ENST00000635120.2	NP_150094.5
CSMD1	XM_011534752.3	c.3631+9946C>A		intron_variant	Intron 23 of 68		XP_011533054.1
CSMD1	XM_017013731.2	c.3631+9946C>A		intron_variant	Intron 23 of 63		XP_016869220.1
CSMD1	XM_011534753.4	c.724+9946C>A		intron_variant	Intron 6 of 52		XP_011533055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSMD1	ENST00000635120.2	c.3631+9946C>A		intron_variant	Intron 23 of 69	5	NM_033225.6	ENSP00000489225.1

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87576 AN: 151942 Hom.: 26637 Cov.: 33

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.656

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.583

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.577 AC: 87693 AN: 152060 Hom.: 26693 Cov.: 33 AF XY: 0.574 AC XY: 42664 AN XY: 74310

African (AFR) AF: 0.762 AC: 31614 AN: 41508

American (AMR) AF: 0.657 AC: 10032 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1777 AN: 3468

East Asian (EAS) AF: 0.647 AC: 3336 AN: 5154

South Asian (SAS) AF: 0.508 AC: 2446 AN: 4818

European-Finnish (FIN) AF: 0.431 AC: 4542 AN: 10546

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.473 AC: 32177 AN: 67970

Other (OTH) AF: 0.584 AC: 1234 AN: 2114

Alfa AF: 0.345 Hom.: 756

Bravo AF: 0.605

Asia WGS AF: 0.625 AC: 2172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.031
DANN	Benign	0.51
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4395910; hg19: chr8-3190870;